Transcranial Magnetic Stimulation to Improve Speech in Aphasia

OBJECTIVE: The purpose of this research is to investigate whether repetitive transcranial
magnetic stimulation (rTMS) can improve speech in chronic stroke patients with aphasia. TMS
allows painless, noninvasive stimulation of brain cortex (1 cm x 1 cm). Slow (1 Hz) rTMS
appears to decrease excitability in the targeted cortical region of interest (ROI) leading
to measurable behavioral effects. Chronic aphasia patients have been observed in our fMRI
work (and others) to have increased activation in right (R) Broca's and other R language
homologues during language tasks. It is hypothesized that suppression of activity in a
directly targeted right hemisphere (RH) ROI will have an overall modulating effect on
functionally connected elements of the distributed neural network for naming (and
propositional speech), and will result in behavioral improvement. Patients are studied with
overt naming fMRI brain scan pre-and post-rTMS at the Boston University Center for
Biomedical Imaging.

RESEARCH PLAN AND METHODS:

The rTMS treatments in Boston take place at the Berenson-Allen Center for Noninvasive Brain
Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School under the
supervision of Alvaro Pascual-Leone, M.D., Ph.D. We plan to study 20 nonfluent aphasia
patients (>6 Mo. poststroke). An additional 20 patients will be studied at the Hospital of
the University of Pennsylvania, H. Branch Coslett, M.D., who is a P.I. on that subcontract.
This is a blinded, randomized, sham-control, incomplete crossover design. Naming and
language tests (and overt naming fMRI scans) are obtained pre- and post- rTMS. All fMRI
scans are covered under the PI's VA Merit Review Grant.

Treatment Design: Multiple Baseline Language Evaluations (x3) are performed at Entry
(Boston Naming Test, BNT; and Boston Diagnostic Aphasia Exam, BDAE). Primary Outcome
Measures are BNT; and Naming subtests and Spontaneous Speech (cookie theft picture
description) from the BDAE. Naming ability for Snodgrass & Vanderwart (S&V, 1980) pictures
is also tested at Baseline. Patients are randomly assigned to receive a series of either
Sham rTMS followed by a series of Real rTMS; OR they receive only the series of Real rTMS.
The Sham series is identical to the Real, however, no magnetic pulse is emitted from the
coil, although the patient hears the same clicking sound emitted from the coil. Due to space
limitation here, only the Real rTMS treatment schedule is described.

There are two rTMS Phases: During Phase 1, the single, best RH cortical ROI to suppress
with rTMS to improve picture naming, is determined for each patient. Real rTMS (1 Hz, 90%
motor threshold) is applied for 10 minutes, in separate rTMS sessions, to each of 4
different RH cortical ROIs (R ant. BA 45; R post. BA 45; R BA 44 and R M1, mouth). S&V
Picture Naming is tested immediately before and after each ROI has been suppressed with
rTMS. The single RH ROI which is associated with at least a 2 SD improvement (above Baseline
S&V Naming), immediately following 10 minutes of rTMS to suppress that cortical area, is
considered to be the Best Response ROI for that patient. We have observed that suppression
of R post. BA 45 to be the Best Response area in 9 previous aphasia cases. During Phase 2,
the Best Response ROI from Phase 1 is suppressed for 20 minutes, 5 days per week, 2 weeks.
All patients receive follow-up BNT and BDAE testing at 2 months following the 10th Real (or
Sham) rTMS treatment.

Inclusion Criteria:

- Right Handed

- Single, Left Hemisphere Cerebrovascular Stroke

- Must be 6 months poststroke onset

- Native Speaker of English

- Clinical Diagnosis of Aphasia

Exclusion Criteria:

- Intracranial metallic body from prior neurosurgical procedure

- Implanted metallic devices: pacemaker, medication pump, vagal stimulator, deep brain
stimulator, TENS unit or ventriculoperitoneal shunt

- Past history of seizure within 1 year

- Pregnancy

- History of substance abuse within last 6 months